Computer Science Faculty Publications

Document Type

Article

Publication Date

8-23-2026

Abstract

Introduction: Early detection of Alzheimer's disease (AD) requires models that combine brain structure changes with genetic risk, but existing methods struggle to align these different data types.

Methods: We present R-GenIMA, an interpretable multimodal large language model that pairs a region-of-interest vision transformer with genetic prompting to jointly analyze structural MRI and single nucleotide polymorphisms (SNPs). Each brain region becomes a visual token and SNP profiles are encoded as structured text, letting the model link regional atrophy to genetic factors through cross-modal attention. Tested on the ADNI cohort, R-GenIMA performs well in classifying four groups: normal cognition, subjective memory concerns, mild cognitive impairment, and AD.

Results: Beyond accuracy, it produces biologically meaningful explanations, identifying stage-specific brain regions and genes. The model consistently highlighted known AD risk genes (APOE, BIN1, CLU, RBFOX1) and revealed stage-specific patterns: striatal involvement in subjective decline, frontotemporal changes in early impairment, and broad network disruption in AD.

Discussion: These results show that interpretable multimodal AI can integrate imaging and genetics to reveal disease mechanisms, providing a foundation for clinical tools that enable earlier risk assessment and inform precision treatment in Alzheimer's disease.

Comments

© 2026 Zhao, Dai, Zhang, Liu, Gu, Lin, Thompson, Leow, Huang, He, Zhan and Tang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Title

Frontiers in Radiology

DOI

10.3389/fradi.2026.1912277

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